Kaempferol alleviates myocardial ischemia injury by reducing oxidative stress via the HDAC3-mediated Nrf2 signaling pathway

作者：Zejun Yue, Yirong Zhang, Wei Zhang, Nanbo Zheng, Jiazheng Wen, Lingxuan Ren, Xiaoyu Rong, Liang Bai, Rong Wang, Sihai Zhao, Enqi Liu, Weirong Wang · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.10.037 · 被引用次数：35 · 研究领域：Genomics, phytochemicals, and oxidative stress、Histone Deacetylase Inhibitors Research、Cardiac Fibrosis and Remodeling

• KAE alleviates myocardial ischemia injury and improves cardiac function in rats. • KAE attenuates myocardial injury and oxidative stress by inhibiting HDAC3. • KAE protects against myocardial ischemia via HDAC3-mediated Nrf2 signaling pathway. Kaempferol (KAE) is a flavonoid found in various plants. Recent studies showed that high dietary intake of KAE was associated with a lower risk of myocardial infarction; however, the cardioprotective mechanism of KAE remains unknown. To determine the effect of KAE on cardiac injury in isoproterenol (ISO)-induced rats and cobalt chloride (CoCl 2 )-treated cardiomyocytes , and the underlying mechanisms. Male rats were pretreated with different doses of KAE for 14 days, and then injected with ISO to induce myocardial ischemia injury. We also established a model of myocardial cell injury using rat H9c2 cardiomyocytes stimulated with CoCl 2 . We found that KAE pretreatment significantly alleviated myocardial injury and improved cardiac function in ISO-injected rats. In addition, KAE reduced oxidative stress in rats with myocardial ischemia by decreasing malondialdehyde concentration and increasing superoxide dismutase activity, and protection of the myocardial mitochondrial structure. KAE also attenuated CoCl 2 -induced injury of H9c2 cardiomyocytes via suppression of oxidative stress. With regard to the mechanism, we found that KAE down-regulated HDAC3 expression and up-regulated Nrf2 expression in ISO-induced rats and CoCl 2 -stimulated ...